Abstract
The potential role of 4-1BB in human immunodeficiency virus (HIV-1)-infected T cells was investigated with HIV-1-infected subjects. 4-1BB expression was readily inducible on PHA stimulation of T cells from HIV-1-infected individuals. The level of 4-1BB expression and the percentage of 4-1BB-expressing T cells were higher in HIV-1+ individuals than in the HIV-1- controls (p < 0.01). The difference in 4-1BB expression was more significant in CD8+ T cells and the high level of 4-1BB expression was correlated with low CD4+ T cell counts (r = -0.63, p < 0.05). 4-1BB signal cooperated with CD28 for proper HIV-1+ CD4+ T cell proliferation. In addition, cross-linking 4-1BB with agonistic monoclonal antibody enhanced HIV-1 replication both in primary stimulation and secondary restimulation of CD4+ T cells from HIV-1+ individuals. To test whether 4-1BB cross-linking signals an activation of HIV-1, J8-1, a 4-1BB+ Jurkat subline, was transiently transfected with pHIV-1-LTR-CAT plasmid and stimulated through 4-1BB. Combined stimulation of 4-1BB and CD3 resulted in an enhanced CAT activity compared with CD3 stimulation alone. Thus, 4-1BB may be involved in the activation of HIV-1 replication from latently infected CD4+ T cells.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Antibodies, Monoclonal / immunology
-
Antigens, CD
-
CD28 Antigens / immunology
-
CD3 Complex / immunology
-
CD4-Positive T-Lymphocytes / immunology
-
CD4-Positive T-Lymphocytes / virology
-
CD8-Positive T-Lymphocytes / immunology
-
Cell Line
-
Chloramphenicol O-Acetyltransferase / genetics
-
Chloramphenicol O-Acetyltransferase / metabolism
-
Gene Expression
-
HIV Infections / immunology
-
HIV Infections / virology*
-
HIV Reverse Transcriptase
-
HIV-1 / physiology*
-
Humans
-
Jurkat Cells
-
Lymphocyte Activation*
-
Receptors, Nerve Growth Factor / genetics
-
Receptors, Nerve Growth Factor / immunology*
-
Receptors, Nerve Growth Factor / physiology*
-
Receptors, Tumor Necrosis Factor / genetics
-
Receptors, Tumor Necrosis Factor / immunology*
-
Receptors, Tumor Necrosis Factor / physiology*
-
Repetitive Sequences, Nucleic Acid
-
Transcription, Genetic
-
Transfection
-
Tumor Necrosis Factor Receptor Superfamily, Member 9
-
Virus Replication
Substances
-
Antibodies, Monoclonal
-
Antigens, CD
-
CD28 Antigens
-
CD3 Complex
-
Receptors, Nerve Growth Factor
-
Receptors, Tumor Necrosis Factor
-
TNFRSF9 protein, human
-
Tumor Necrosis Factor Receptor Superfamily, Member 9
-
Chloramphenicol O-Acetyltransferase
-
HIV Reverse Transcriptase